P2Y12 inhibitors in neuroendovascular surgery: An opportunity for precision medicine.

INTRODUCTION: Dual antiplatelet therapy (DAPT), primarily the combination of aspirin with a P2Y12 inhibitor, in patients undergoing intravascular stent or flow diverter placement remains the primary strategy to reduce device-related thromboembolic complications. However, selection, timing, and dosing of DAPT is critical and can be challenging given the existing significant inter- and intraindividual response variations to P2Y12 inhibitors. METHODS: Assessment of indexed, peer-reviewed literature from 2000 to 2020 in interventional cardiology and neuroendovascular therapeutics with critical, peer-reviewed appraisal and extraction of evidence and strategies to utilize DAPT in cardio- and neurovascular patients with endoluminal devices. RESULTS: Both geno- and phenotyping for DAPT are rapidly and conveniently available as point-of-care testing at a favorable cost-benefit ratio. Furthermore, systematic inclusion of a quantifying clinical risk score combined with an operator-linked, technical risk assessment for potential adverse events allows a more precise and individualized approach to new P2Y12 inhibitor therapy. CONCLUSIONS: The latest evidence, primarily obtained from cardiovascular intervention trials, supports that combining patient pharmacogenetics with drug response monitoring, as part of an individually tailored, precision medicine approach, is both predictive and cost-effective in achieving and maintaining individual target platelet inhibition levels. Indirect evidence supports that this gain in optimizing drug responses translates to reducing main adverse events and overall treatment costs in patients undergoing DAPT after intracranial stent or flow diverting treatment.

Lower complication rates associated with transradial versus transfemoral flow diverting stent placement.

BACKGROUND: Currently, there are no large-scale studies in the neurointerventional literature comparing safety between transradial (TRA) and transfemoral (TFA) approaches for flow diversion procedures. This study aims to assess complication rates in a large multicenter registry for TRA versus TFA flow diversion. METHODS: We retrospectively analyzed flow diversion cases for cerebral aneurysms from 14 institutions from 2010 to 2019. Pooled analysis of proportions was calculated using weighted analysis with 95% CI to account for results from multiple centers. Access site complication rate and overall complication rate were compared between the two approaches. RESULTS: A total of 2,285 patients who underwent flow diversion were analyzed, with 134 (5.86%) treated with TRA and 2151 (94.14%) via TFA. The two groups shared similar patient and aneurysm characteristics. Crossover from TRA to TFA was documented in 12 (8.63%) patients. There were no access site complications in the TRA group. There was a significantly higher access site complication rate in the TFA cohort as compared with TRA (2.48%, 95% CI 2.40% to 2.57%, vs 0%; p=0.039). One death resulted from a femoral access site complication. The overall complications rate was also higher in the TFA group (9.02%, 95% CI 8.15% to 9.89%) compared with the TRA group (3.73%, 95% CI 3.13% to 4.28%; p=0.035). CONCLUSION: TRA may be a safer approach for flow diversion to treat cerebral aneurysms at a wide range of locations. Both access site complication rate and overall complication rate were lower for TRA flow diversion compared with TFA in this large series.

Correction to: Standards for Neurologic Critical Care Units: A Statement for Healthcare Professionals from The Neurocritical Care Society.

The authors note that there is a discrepancy between the text of the paper and Table 2 regarding physician subspecialty certification requirements in neurocritical care for Level II centers.

Standards for Neurologic Critical Care Units: A Statement for Healthcare Professionals from The Neurocritical Care Society.

Neurocritical care is a distinct subspecialty focusing on the optimal management of acutely ill patients with life-threatening neurologic and neurosurgical disease or with life-threatening neurologic manifestations of systemic disease. Care by expert healthcare providers to optimize neurologic recovery is necessary. Given the lack of an organizational framework and criteria for the development and maintenance of neurological critical care units (NCCUs), this document is put forth by the Neurocritical Care Society (NCS). Recommended organizational structure, personnel and processes necessary to develop a successful neurocritical care program are outlined. Methods: Under the direction of NCS Executive Leadership, a multidisciplinary writing group of NCS members was formed. After an iterative process, a framework was proposed and approved by members of the writing group. A draft was then written, which was reviewed by the NCS Quality Committee and NCS Guidelines Committee, members at large, and posted for public comment. Feedback was formally collated, reviewed and incorporated into the final document which was subsequently approved by the NCS Board of Directors.

Paradoxical cerebrovascular hemodynamic changes with nicardipine.

OBJECTIVE Intravenous nicardipine is commonly used for blood pressure reduction in patients with acute stroke. However, few studies have described its effects on cerebrovascular hemodynamics as measured by transcranial Doppler (TCD) waveform analysis and pulsatility index (PI). In this study, the authors report examples of a consistent but paradoxical finding associated with nicardipine that suggests intracranial vasoconstriction, contrary to what is expected from a vasodilator. METHODS The data presented are from a convenience sample of patients who underwent TCD monitoring before, after, or during nicardipine administration. In each case, TCD waveform morphologies and PIs were compared. RESULTS The TCD waveforms during nicardipine infusion are characterized by a prominent systolic peak and dicrotic notch. Systolic deceleration was more pronounced and PIs were significantly elevated in patients who were on nicardipine (p < 0.001). This finding was not evident when patients were not on nicardipine. CONCLUSIONS This study provides the first evidence of paradoxical intracranial vasoconstriction associated with intravenous nicardipine. In the authors' experience, this finding is consistently encountered in the vast majority of patients who are treated with intravenous nicardipine, and is contradictory to what is expected from a vasodilator. Future studies are needed to confirm this finding in larger populations and diverse clinical settings and to examine mechanisms that explain this phenomenon.

Angioinvasive Aspergillus-associated Stroke in an Immunocompetent Host Following Cardiac Surgery and ECMO.

INTRODUCTION: Invasive cerebral aspergillosis is an uncommon cause of stroke among immunocompetent patients and has not been reported in association with cardiac surgery or extracorporeal membrane oxygenation (ECMO). We report the case of an immunocompetent host who developed aspergillus-associated stroke following coronary artery bypass graft (CABG) and ECMO. CASE REPORT: A 59-year-old woman developed cardiogenic shock after 3-vessel-CABG requiring intra-aortic balloon pump placement and subsequent veno-arterial ECMO. Noncontrast computed tomography of the brain was suggestive of multiple bihemispheric ischemic infarcts. Postmortem pathologic analysis revealed aspergillus-associated inflammation of blood vessels and ischemic and petechial hemorrhagic strokes in the affected territories. DISCUSSION AND CONCLUSIONS: Ischemic infarcts in the setting of CABG or ECMO are often presumed to be thromboembolic from the heart or device, related to underlying hemodynamic instability, or due to a clinically apparent systemic infection such as endocarditis. This report suggests that invasive cerebral aspergillosis should be considered in seemingly immunocompetent patients following CABG or ECMO. The mechanism is unclear, but may be related to systemic inflammatory dysregulation resulting in increased susceptibility to uncommon pathogens.

Neurological Prognostication of Cardiac Arrest in an Era of Extracorporeal Membrane Oxygenation.

A neuron-specific enolase level greater than 33 ng/mL at days 1 to 3 or status myoclonus within 1 day are traditional indicators of poor neurological prognosis in survivors of cardiac arrest. We report the case of a 70-year-old man who received extracorporeal membrane oxygenation following cardiac arrest. Despite having both an elevated neuron-specific enolase concentration of 68 ng/mL and status myoclonus, he made an excellent neurological recovery. The value of traditional markers of poor prognosis such as elevated neuron-specific enolase or status myoclonus has not been systematically validated in patients treated with extracorporeal membrane oxygenation or therapeutic hypothermia. Straightforward application of practice guidelines in these cases may result in tragic outcomes. This case underscores the need for reliable prognostic markers that account for recent advances in cardiopulmonary and neurological therapies.

Systematic Quality Assessment of Published Antishivering Protocols.

Shivering is a common side effect of targeted temperature modulation and general anesthesia. Antishivering strategies often employ a stepwise approach involving both pharmacological and physical interventions. However, approaches to treat shivering are often empiric and vary widely across care environments. We evaluated the quality of published antishivering protocols and guidelines with respect to methodological rigor, reliability, and consistency of recommendations.Using 4 medical databases, we identified 4027 publications that addressed shivering therapy, and excluded 3354 due to lack of relevance. After applying predefined eligibility criteria with respect to minimal protocol standards, 18 protocols/guidelines remained. Each was assessed using a modified Appraisal of Guidelines for Research and Evaluation II (mAGREE II) instrument containing 23 quality items within 6 domains (maximal score 23). Among 18 protocols/guidelines, only 3 incorporated systematically reviewed recommendations, whereas 15 merely targeted practice standardization. Fifteen of 18 protocols/guidelines addressed shivering during therapeutic cooling in which skin counterwarming and meperidine were most commonly cited. However, their mAGREE II scores were within the lowest tertile (1 to 7 points) and the median for all 18 protocols was 5. The quality domains most commonly absent were stakeholder involvement, rigor of development, and editorial independence. Three of 18 protocols/guidelines addressed postanesthetic antishivering. Of these, the American Society of Anesthesiologists guidelines recommending forced-air warming and meperidine received the highest mAGREE II score (14 points), whereas the remaining 2 recommendations had low scores (<5 points).Current published antishivering protocols/guidelines lack methodological rigor, reliability, and strength, and even the highest scoring of the 18 protocols/guidelines fulfilled only 60% of quality items. To be consistent with evidence-based protocol/guideline development processes, future antishivering treatment algorithms should increase methodological rigor and transparency.

Optimizing Outcomes for Mechanically Ventilated Patients in an Era of Endovascular Acute Ischemic Stroke Therapy.

Endovascular mechanical thrombectomy is a new standard of care for acute ischemic stroke (AIS). The majority of these patients receive mechanical ventilation (MV), which has been associated with poor outcomes. The implication of this is significant, as most neurointerventionalists prefer general compared to local anesthesia during the procedure. Consequences of hemodynamic and respiratory perturbations during general anesthesia and MV are thought to contribute significantly to the poor outcomes that are encountered. In this review, we first describe the unique risks associated with MV in the specific context of AIS and then discuss evidence of brain goal-directed approaches that may mitigate these risks. These strategies include an individualized approach to hemodynamic parameters (eg, adherence to a minimum blood pressure goal and adequate volume resuscitation), respiratory parameters (eg, arterial carbon dioxide optimization), and the use of ventilator settings that optimize neurological outcomes (eg, arterial oxygen optimization).

Pentobarbital-Induced Myocardial Stunning in Status Epilepticus Requiring Extracorporeal Membrane Oxygenation: A Case Report and Literature Review.

Introduction. Mild hypotension is a well-recognized complication of intravenous pentobarbital; however fulminant cardiopulmonary failure has not been previously reported. Case Report. A 28-year-old woman developed pentobarbital-induced cardiopulmonary failure that was successfully treated with maximal medical management including arteriovenous extracorporeal membrane oxygenation. She made an excellent cardiopulmonary and neurological recovery. Discussion and Conclusion. Pentobarbital is underrecognized as a potential cause of myocardial stunning. The mechanism involves direct myocardial depression and inhibition of autonomic neuroanatomical structures including the medulla and hypothalamus. Early recognition and implementation of aggressive cardiopulmonary support are essential to optimize the likelihood of a favorable outcome.

Transcranial Doppler Changes in Patients Treated with Extracorporeal Membrane Oxygenation.

BACKGROUND: Transcranial Doppler (TCD) has significant implications for neurovascular assessment in patients being treated with venoarterial-extracorporeal membrane oxygenation (VA-ECMO). However, there have been no studies demonstrating the changes in pulsatility indices (PIs) seen in these patients. Nonpulsatile waveforms are seen during on-pump coronary artery bypass graft, but low or low-normal PIs have never been reported. It is important to be aware of these changes, as they can be misinterpreted as cerebral vasodilation, vasoconstriction, increased intracranial pressures (ICPs), or cerebral circulatory arrest. METHODS: Data from 11 TCDs from 8 patients on VA-ECMO in the Cedars Sinai Medical Center Cardiac Surgical Intensive Care Unit were reviewed. Mean pulsatility indices were calculated for each patient using Gosling's PI formula. The values obtained were correlated with ejection fraction (EF) values obtained from a transthoracic or transesophageal echocardiogram. RESULTS: PIs were globally low or absent in all 11 TCDs. In 3 patients, TCDs were performed at the initiation and conclusion of the VA-ECMO cannulation. The PI values for these TCDs correlated directly with changes in EFs. Also, an abrupt rise in PI to normal value was seen with the placement of a total artificial heart and the return of pulsatile circulation. CONCLUSIONS: We demonstrate that PIs on TCDs in patients treated with VA-ECMO are either low or cannot be calculated depending on the severity of myocardial suppression, and should not be mistaken for cerebral vasodilation or cerebral circulatory arrest. Moreover, rising PIs in these patients can represent improving cardiac function and should not be confused with elevated ICPs.

Hospital Readmission Rates Among Mechanically Ventilated Patients With Stroke.

BACKGROUND AND PURPOSE: Tracheostomy is frequently performed in patients with severe ischemic stroke, intracerebral hemorrhage, or subarachnoid hemorrhage. Little is known about readmission rates among stroke patients who undergo mechanical ventilation. METHODS: We used previously validated International Classification of Diseases, Ninth Edition-Clinical Modification codes and data on all discharges from nonfederal acute care hospitals in 3 states. We compared readmission rates among mechanically ventilated patients with stroke who were discharged with or without a tracheostomy. RESULTS: Among 39,881 patients who underwent mechanical ventilation during the index stroke hospitalization and survived to discharge, 10,690 (26.8%; 95% confidence interval, 26.4%-27.2%) underwent tracheostomy. During a mean follow-up period of 3.4 (±2.0) years, the overall incidence rate of readmissions was 4.25 (95% confidence interval, 4.22-4.28) per 100 patients per 30 days. The rate of any readmissions within 30 days was 26.9% among patients with tracheostomy compared with 22.5% among those without a tracheostomy (absolute risk difference, 4.4%; 95% confidence interval, 3.5%-5.4%; P<0.001). After adjustment for potentially confounding variables, tracheostomy was associated with a slightly increased readmission rate (incidence rate ratio, 1.07; 95% confidence interval, 1.03-1.11). CONCLUSIONS: Approximately one quarter of mechanically ventilated patients with stroke who survive to discharge are readmitted to the hospital within 30 days. Readmission rates are significantly higher in patients with stroke who undergo tracheostomy, but the difference is not clinically meaningful. Thirty-day readmission rates among mechanically ventilated patients with stroke are similar to Medicare beneficiaries hospitalized with major medical diseases such as pneumonia.

Efficacy of Nonpharmacological Antishivering Interventions: A Systematic Analysis.

OBJECTIVE: We performed a systematic review of the published evidence regarding nonpharmacologic antishivering interventions in various clinical settings. DATA SOURCES: Studies through November 2014 were identified using predefined search terms in electronic databases, including PubMed, the Cochrane Library, EMBASE: Excerpta Medica (Ovid), and Web of Science. STUDY SELECTION: All identified articles were critically analyzed by applying prespecified criteria. We included experimental trials with comparable baseline data investigating the antishivering efficacy of nonpharmacological interventions in subjects without underlying thermoregulatory dysfunction. DATA EXTRACTION: Sixty-five publications (3,361 subjects) were analyzed by the type of clinical setting, intervention, comparison, and study design. In addition, each study underwent a standardized study quality assessment. DATA SYNTHESIS: Nonpharmacological interventions consisted of active cutaneous warming (forced-air warming, electric heating pad/blanket, radiant heating, and water-circulating mattress), body core warming (fluid or gas warming system), passive cutaneous warming (space blankets or towels), and electroacupuncture. Identified clinical settings included perioperative settings without induced hypothermia (60 of 77 comparisons), perioperative settings with induced hypothermia (8 of 77), and induced hypothermia without anesthesia (9 of 77). Active cutaneous warming was the most commonly studied intervention, and it was associated with the highest prevalence of positive results when compared with controls in all three clinical settings. In contrast, passive cutaneous warming and body core warming showed conflicting efficacy. Comparison evaluations among different antishivering interventions were limited due to the paucity and heterogeneity of studies directly comparing different interventions against one another. CONCLUSION: This systematic review of the effectiveness of nonpharmacological antishivering methods delineates active cutaneous warming as the most effective nonpharmacologic antishivering intervention in the perioperative and induced hypothermia settings.

Effect of early mobilization on sedation practices in the neurosciences intensive care unit: a preimplementation and postimplementation evaluation.

INTRODUCTION: The use of sedation and analgesia protocols, daily interruption of sedation, and early mobilization (EM) have been shown to decrease duration of mechanical ventilation and hospital length of stay (LOS). METHODS: A retrospective chart review was conducted during a 6-month premobilization (pre-EM) and 6-month postmobilization (post-EM) period. Patients older than 18 years who were admitted to the neurosciences intensive care unit (ICU) and mechanically ventilated for at least 24 hours without documentation of withdrawal of life support or brain death were included. RESULTS: Thirty-one pre-EM and 37 post-EM patients were included. Baseline demographics were similar with the exception of more ischemic stroke patients in the pre-EM group (P < .05). In the pre-EM and post-EM groups, patients received similar cumulative doses of propofol, dexmedetomidine, and benzodiazepines but higher median (interquartile range) doses of opioids (50.0 [13.8-165.0] vs 173.3 [41.2-463.2] µg of fentanyl equivalents [P < .05]) in the post-EM group. Neurosciences ICU LOS was 10 (6-19) and 13 (8-18) days, respectively (P = .188). CONCLUSIONS: After implementation of an EM program, an increase in opioid use and no significant change in other sedatives were observed. Despite an increase in the amount of physical therapy and occupational therapy provided to patients, there was no change in hospital and ICU LOS or duration of mechanical ventilation.

Mechanical Ventilation for Acute Stroke: A Multi-state Population-Based Study.

BACKGROUND: Mechanical ventilation is frequently performed in patients with ischemic stroke (IS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). In this study, we used statewide administrative claims data to examine the rates of use, associated conditions, and in-hospital mortality rates for mechanically ventilated stroke patients. METHODS: We used statewide administrative claims data from three states and ICD-9-CM codes to identify patients admitted with stroke and those who received mechanical ventilation and tracheostomy. Descriptive statistics and exact 95 % confidence intervals were used to report rates of mechanical ventilation, tracheostomy, and in-hospital mortality. Logistic regression analysis was performed to identify conditions associated with mechanical ventilation based on previously described risk factors. RESULTS: 798,255 hospital admissions for stroke were identified. 12.5 % of these patients underwent mechanical ventilation. This rate varied by stroke type: 7.9 % for IS, 29.9 % for ICH, and 38.5 % for SAH. Increased age was associated with a decreased risk of receiving mechanical ventilation (RR per decade, 0.91). Of stroke patients who underwent mechanical ventilation, 16.3 % received a tracheostomy. Mechanical ventilation was more likely to occur in association with status epilepticus (RR, 5.1), pneumonia (RR, 4.9), sepsis (RR, 3.6), and hydrocephalus (RR, 3.3). In-hospital mortality rate for mechanically ventilated stroke patients was 52.7 % (46.8 % for IS, 61.0 % for ICH, and 54.6 % for SAH). CONCLUSIONS: In this large population-based sample, over half of mechanically ventilated stroke patients died in the hospital despite the fact that younger patients were more likely to receive mechanical ventilation. Future studies are indicated to elucidate mechanical ventilation strategies to optimize long-term outcomes after severe stroke.

A 59-year-old man with acute onset of paralysis.

Botulism is a neuroparalytic illness resulting from the action of a potent toxin produced by the organism Clostridium botulinum. It can present with a classic triad of clear mentation, bulbar palsy and symmetric descending paralysis. Treatment is symptomatic and includes a botulinum antitoxin.

Hemicraniectomy and durotomy upon deterioration from infarction-related swelling trial: randomized pilot clinical trial.

BACKGROUND AND PURPOSE: Hemicraniectomy and Durotomy Upon Deterioration From Infarction-Related Swelling Trial (HeADDFIRST) was a randomized pilot study to obtain information necessary to design a Phase III trial to evaluate the benefit of surgical decompression for brain swelling from large supratentorial cerebral hemispheric infarction. METHODS: All patients with stroke were screened for eligibility (age 18-75 years, National Institutes of Health Stroke Scale≥18 with Item 1a<2 [responsive to minor stimulation], and CT demonstrating unilateral, complete middle cerebral artery territory infarction by specific imaging criteria). All enrolled patients were treated using a standardized medical treatment protocol. Those with both≥4 mm of pineal shift and deterioration in level of arousal or ≥7.5 mm of anteroseptal shift within 96 hours of stroke onset were randomized to continued medical treatment only or medical treatment plus surgery. Death at 21 days was the primary outcome measure. RESULTS: Among 4909 screened patients, only 66 (1.3%) patients were eligible for HeADDFIRST. Forty patients were enrolled, and 26 patients developed the requisite brain swelling for randomization. All who failed to meet randomization criteria were alive at 21 days. Mortality at 21 and 180 days was 40% (4/10) in the medical treatment only and 21% (3/14) and 36% (5/14) in the medical treatment plus surgery arms, respectively. CONCLUSIONS: HeADDFIRST randomization criteria effectively distinguished low from high risk of death from large supratentorial cerebral hemispheric infarction. Lower mortality in the medical treatment only group than in other published trials suggests a possible benefit to standardizing medical management. These results can inform the interpretation of recently completed European trials concerning patient selection and medical management. CLINICAL TRIAL REGISTRATION: This trial was not registered because enrollment began before July 1, 2005.

A young man with altered mental status and new-onset seizures.

Signs and symptoms of a subacute, progressive, imaging-negative encephalopathy can be misdiagnosed as a neuropsychiatric or progressive neurodegenerative disorder. However, encephalopathies often can be reversed if the autoimmune component is recognized early through a careful history and diagnostic testing, including cerebrospinal fluid analysis for antibodies.

Depressed mood and quality of life after subarachnoid hemorrhage.

BACKGROUND: Cognitive impairment is widely considered the main cause of disability and handicap after subarachnoid hemorrhage (SAH). The impact of depression on recovery after SAH remains poorly defined. We sought to determine the frequency of post-SAH depression, identify risk factors for its development, and evaluate the impact of depression on quality of life (QOL) during the first year of recovery. METHODS: We prospectively studied 216 of 534 SAH patients treated between July 1996 and December 2001 with complete one-year follow-up data. Depression was evaluated with the Center for Epidemiological Studies Depression (CES-D) scale, cognitive status with the Telephone Interview for Cognitive Status (TICS), and QOL with the Sickness Impact Profile (SIP) 3 and 12 months after SAH. RESULTS: Depressed mood occurred in 47% of patients during the first year of recovery; 26% were depressed at both 3 and 12 months. Non-white ethnicity predicted early (3 month) and late (12 month) depressions; early depression was also predicted by previously-diagnosed depression, cigarette smoking, and cerebral infarction, whereas late depression was predicted by prior social isolation and lack of medical insurance. Depression was associated with inferior QOL in all domains of the SIP, and changes in depression status were associated with striking parallel changes in QOL, disability, and cognitive function during the first year of recovery. CES-D scores accounted for over 60% of the explained variance in SIP total scores, whereas TICS performance accounted for no more than 6%. CONCLUSION: Depression affects nearly half of SAH patients during the first year of recovery, and is associated with poor QOL. Systematic screening and early treatment for depression are promising strategies for improving outcome after SAH.